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Biomedical subjects

M Nilsson

Publications and source records attributed to M Nilsson.

At least 271 records · Page 15Linked to original sources

Graded response in the individual thyroid follicle cell to increasing doses of TSH.

The in vivo activation of rat thyroid follicle cells by increasing doses of TSH (1-100 mU) was studied by quantitative light and electron microscopy. The number of pseudopods induced after 20 min by 5, 20, 50 and 100 mU was the same but a dose-dependent increment of the individual pseudopod size (measured as profile area or membrane surface area) was observed, suggesting a graded response in the individual follicle cell. The number of pseudopods induced by 1 mU was only 10% of that in the other group. Another early effect of TSH, besides the induction of psuedopods, is stimulation of exocytosis. The number of exocytotic vesicles in pseudopod-bearing follicle cell profiles (the presence of a pseudopod taken as a sign of activation) decreased in a dose-dependent manner. This indicates that the follicle cell does not respond in an all-or-none mode (in which case a similar decrease in vesicle number in activated cells should be expected irrespective of the level of TSH) and that the response in the individual cell is graded depending on the level of TSH stimulation.

Animals↗

Comparison of measured and calculated absorbed doses from tangential irradiation of the breast.

Calculated absorbed dose distributions from tangential irradiation of the breast have been compared with TLD measurements in a anthropomorfic body-shaped phantom which has gone through all phases of the radiation treatment planning cycle, including mapping of electron densities with a CT scanner, simulation of beam set-up and several treatments with an accelerator. The absorbed doses, measured in the breast are 2-6% lower than those calculated with the clinically used treatment planning system. The deviation is slightly higher when wedges are used. The main source for this deviation is shown to be the limitations in the loss-of-scatter correction in the dose calculation algorithm used. It has also been noted that the variation of the absorbed dose in the target volume is in general smaller than predicted by the calculations.

Breast Neoplasms↗

A method for conversion of Hounsfield number to electron density and prediction of macroscopic pair production cross-sections.

A method for the determination of electron density using a narrow beam attenuation geometry is described. The method does not require that the elemental composition of the phantom materials is known. The Hounsfield numbers for the phantom materials used were determined using five different CT scanners. A relationship between Hounsfield number and electron density can thus be established, which is of considerable value in radiation therapy treatment planning procedures. Measurements of the ratio coherent/incoherent scattering of low energy photons in a certain geometry has proven valuable for determination of atomic number, which in its turn can be used for estimation of macroscopic pair production coefficients for high energy photons. The combination of knowledge of electron density with methods for determination of processes, dependent on atomic number, can form a base for adequate composition of phantom materials for purposes of testing dose calculation algorithms for photons and electrons.

Electrons↗

Increased levels of several retinoid binding proteins resulting from retinoic acid-induced differentiation of F9 cells.

The embryonal carcinoma cell line F9 is known to differentiate when exposed to retinoic acid. We have examined the quantities of two intracellular retinoid-binding proteins in undifferentiated and differentiated F9 cells. The existence of a cell surface receptor that recognizes the plasma retinol-binding protein was also explored. It was shown that undifferentiated F9 cells contain low concentrations of the two retinoid-binding proteins. The cellular retinoic acid-binding protein was present in approximately 3-fold molar excess over the cellular retinol-binding protein. Upon culture in the presence of retinoic acid, F9 cells display elevated concentrations of both cellular retinol-binding protein and cellular retinoic acid-binding protein. Since the levels of beta 2-microglobulin, a marker of the differentiated state with no known involvement in the metabolism of vitamin A, increased in parallel with the retinoid-binding proteins, it seems unlikely that retinoic acid selectively increased the levels of the two retinoid-binding proteins. The differentiated, in contrast to the undifferentiated cells, can accumulate retinol from plasma retinol-binding protein and display a cell surface receptor for this protein. Despite the fact that retinoic acid-induced differentiation of F9 cells promotes increased levels of several proteins involved in the normal metabolism of vitamin A, no evidence was obtained to suggest that the cells were dependent on retinoids to maintain their differentiated state.

Animals↗

Synthesis of the methyl and 1-octyl glycosides of the P-antigen tetrasaccharide (globotetraose).

The methyl and 1-octyl beta-glycosides of the P-antigen tetrasaccharide [globotetraose, beta-D-GalpNAc-(1----3)-alpha-D-Galp-(1----4)-beta-D-Galp-(1----4) -D-Glc] were synthesised from a tetrasaccharide precursor, prepared using methyl disaccharide 1-thioglycosides as intermediates. In the key glycosidation with silver triflate, HO-2 was used as an alpha-directing group in the glycosyl bromide.

Carbohydrate Conformation↗

Cellular retinoid binding proteins.

The cellular retinol-binding protein (CRBP) and the cellular retinoic acid binding protein (CRABP) have similar physicochemical characteristics. The amino acid sequences of rat CRBP and bovine CRABP have been elucidated and they display 40% sequence identity. Both protein sequences appear to be evolutionarily highly conserved. The amino acid sequence of human CRBP, deduced from a cDNA-clone, is 96% identical to the rat CRBP sequence. CRBP and CRABP are members of a protein family, all members of which may bind hydrophobic ligands and interact with membrane components. All members of the protein family are probably related in tertiary structure and might interact with membrane components through two regions with a high probability for alpha-helix. The tissue distribution of CRBP and CRABP, together with their relation to lipid transporting proteins suggests that CRBP and CRABP are cellular transporting proteins for retinol and retinoic acid, respectively.

Amino Acid Sequence↗

Cloning and sequencing of a full length cDNA corresponding to human cellular retinol-binding protein.

We have isolated and sequenced a cDNA clone corresponding to the human cellular retinol-binding protein (CRBP). The deduced amino acid sequence, which encompasses 134 amino acid residues, shows significant homology with several low molecular weight proteins which bind hydrophobic ligands. No homology to the plasma retinol-binding protein was observed. Southern and Northern blot analyses suggest that the CRBP gene is present in a single copy in the haploid genome and that it is transcribed in a single mRNA species.

Amino Acid Sequence↗

Amino acid and monoamine transport in primary astroglial cultures from defined brain regions.

The uptake of L-[3H]glutamate, L-[3H]aspartate, gamma-[3H]aminobutyric acid (GABA), [3H]dopamine, DL-[3H]norepinephrine and [3H]5-hydroxytryptamine (5-HT) was studied in astrocytes cultured from the cerebral cortex, striatum and brain stem of newborn rat and grown for 2 weeks in primary cultures. The astrocytes exhibited a high-affinity L-glutamate uptake with Km values ranging from 11 to 110 microM. Vmax values were 4.5 in cerebral cortex, 39.1 in striatum, and 0.4 in brain stem, nmol per mg cell protein per min. There was a less prominent high-affinity uptake of L-aspartate with Km values from 88 to 187 microM. Vmax values were 7.4 in cerebral cortex, 37.1 in striatum, and 3.1 in brain stem, nmol per mg cell protein per min. The high-affinity GABA uptake exhibited Km values ranging from 5 to 17 microM and Vmax values were 0.01 for cerebral cortex, 0.04 for striatum, and 0.1 for brain stem, nmol per mg cell protein per min. No high-affinity, high-capacity uptake was found for the monoamines. The results demonstrate a heterogeneity among the astroglial cells cultivated from the different brain regions concerning the uptake capacity of amino acid neurotransmitters. Furthermore, amino acid transmitters and monoamines are taken up by the cells in different ways.

Amino Acids↗

Gamma camera evaluation of the effects of degradable starch microspheres on arterial liver blood flow in the rat.

Degradable starch microspheres injected into an artery causes a temporary reduction of regional blood flow and improves the exposure of the organ to a drug injected simultaneously. The purpose of this study was to quantify this effect when microspheres are injected arterially into the liver of rats. As model substance radioactive pertechnetate ions (99TcmO4-) was used. The results were evaluated from external gamma camera measurements. The amounts of microspheres injected together with pertechnetate was 1.5-12 mg. When compared to injections of pertechnetate only, the integrated exposure of the liver to pertechnetate was increased by a factor of 1.4-2.4 when microspheres were added.

Animals↗

The quantitation of C3d by routine methods after the direct absorption of human plasma with anti-C3c.

The immunological methods for quantitating C3d in plasma require first the removal of less fragmented intermediates as well as the intact C3. We describe an alternative method for the quantitation of C3d in human plasma. The components which should be removed are absorbed (precipitated) directly in the plasma by a specific anti-C3c antiserum. It is then possible to determine the concentration of C3d by routine immunological methods.

Antibodies↗

Ornithine decarboxylase activity and polyamines in the anterior pituitary gland during the rat oestrous cycle.

The biosynthesis of polyamines, an ubiquitous group of amines shown to be essential for normal cellular growth and differentiation, was studied in the rat anterior pituitary gland during the different stages of the oestrous cycle. The activity of ornithine decarboxylase (ODC), which catalyses the rate-limiting step in the biosynthesis of polyamines, was low during oestrus, metoestrus and dioestrus. However, a marked transitory rise in ODC activity was found in the pituitary gland on the evening of pro-oestrus. The rise in ODC activity was accompanied by an increase in the pituitary content of the polyamines putrescine and spermidine. Ovariectomy did not significantly change the basal ODC activity in the pituitary gland. Oestrogen treatment of ovariectomized rats resulted in a marked stimulation of pituitary polyamine biosynthesis. The largest effects were observed when oestrogen was given as two injections 72 h apart, which gave rise to levels of ODC activity comparable to those observed on the evening of pro-oestrus. The increase in polyamine synthesis in the anterior pituitary gland during pro-oestrus appeared not to be related to the preovulatory secretion of LH or prolactin, since neither LH-releasing hormone nor thyrotrophin-releasing hormone (which induces a secretion of prolactin) affected pituitary ODC activity. The observed biosynthesis of polyamines may be associated with the cellular proliferation which occurs in the anterior pituitary gland at oestrus.

Animals↗

In vivo shedding of apical plasma membrane in the thyroid follicle cells of the mouse.

Clusters of luminal dense bodies, limited by a triple-layered membrane, were found in all follicle lumina in thyroid glands of mice. After thyroxine treatment the number of luminal dense bodies increased, especially in the periphery of the lumen, where the intraluminal bodies often displayed a striking resemblance to microvilli. In hyperplastic goiters, obtained by feeding mice with propylthiouracil, luminal dense bodies were replaced by intraluminal vesicles. During goiter involution the vesicles were gradually replaced by luminal dense bodies; the presence of intermediate forms suggests that vesicles and dense bodies are basically the same formations. Luminal dense bodies were observed in colloid droplets indicating their removal by endocytosis. As demonstrated by electron-microscopic cytochemistry, luminal dense bodies contain a membrane-bound peroxidase, and electron-microscopic autoradiography after administration of 125I indicate that they possess an iodinating capacity. Our observations on mouse thyroid glands suggest that the luminal dense bodies, which appear as vesicles in hyperplastic glands, are formed by shedding of the apical plasma membrane of the follicle cell. The shedding process might be of importance for the turnover of plasma-membrane material.

Animals↗

UV irradiation and cutaneous vitamin A: an experimental study in rabbit and human skin.

The effect of UV irradiation on the concentration of cutaneous retinoids (retinol and 3-dehydroretinol) in rabbit skin in vivo and in human skin in vitro was investigated. Irradiation with 4 different narrow-wavelength bands produced dose-dependent reductions of retinol in epidermis and dermis. The maximal effect was obtained at 334 nm, a wavelength which coincides with the absorption maximum for retinol in organic solutions. 3-Dehydroretinol was not reduced to the same extent as was retinol. In human skin the photodecomposition of retinol was most extensive in epidermis and progressively less so in dermis, presumably reflecting the extent to which 334 nm radiation penetrates the tissue. The regeneration of cutaneous retinol took over a week in the rabbit. The nutritional and biologic implications of the UV-induced reduction of cutaneous retinol remain to be established.

Animals↗

Structure and tissue distribution of some retinoid-binding proteins.

Vitamin A has, apart from its function in the visual pigments, general effects on several organs. Early signs of vitamin A deficiency include keratinization of epithelia and hyperkeratosis of the skin. To elucidate a generalized function for vitamin A, we have taken the approach of tracing the vitamin from its storage site in the liver via its blood transport by the retinol-binding protein (RBP) to its uptake by susceptible cells. We have also examined the intracellular occurrence of vitamin A as regards its binding to specific receptor proteins. Here we summarize data on the amino acid sequences of several vitamin A-binding proteins. The finding that CRBP and CRABP, the two intracellular proteins, are homologous to each other, to a myelin protein, and to a fatty acid-binding protein may shed light on the functions of these proteins. Retinoic acid, which binds to CRABP but not CRBP, induces differentiation of teratocarcinoma cells. This is accompanied by a lowering of the CRABP concentration, an increase of the CRBP level, and an increase in the uptake of retinol from RBP. The epidermis contains both CRBP and CRABP, and their distributions are rather similar. However, in contrast to CRBP, CRABP is most abundant in cells lining the hair follicles. CRBP occurs in greatest relative amounts in the outer layers of the epidermis. Since techniques have been developed to measure CRBP and CRABP, normal and disease-affected skin may now be explored as to quantity and cellular distribution of the retinoid-binding proteins.

Amino Acid Sequence↗

Thallium-201: autoradiography in pigmented mice and melanin-binding in vitro.

Autoradiography with 201Tl+ in C57Bl mice showed a strong labelling of the eye melanin and of pigmented hair follicles. An analysis of the affinity of thallium for pigment from cow eyes indicated a binding to three groups of sites and showed a marked sensitivity to the addition of H+-ions. The results are consistent with the conception that a binding of thallium occurs to the free carboxyl groups of the melanin and that the structure of the polymer has a marked influence on the affinity. Similar results have previously been obtained with other cations. There was no indication that the strong in vivo affinity of thallium to melanin is due to a more firm binding than for other cations which do not localize on melanin in vivo. Instead, the ability of cations to pass the melanocyte membranes and reach the melanin granules is probably decisive to whether a melanin binding will take place in vivo. Toxic effects on the eye and epilation are symptoms of thallium intoxication which may be related to its melanin binding. The fate of 201Tl+ in some other tissues is also described and discussed.

Animals↗

Venous emptying from the calf. Methodologic report and effect of intermittent pneumatic compression.

In 17 patients undergoing surgery for varicose veins of the leg, the elimination rate of 99Tcm-macroaggregated albumin from the calf of the contralateral leg was studied. The leg had no discernible varicosities. This substance has not previously been used in such a context. Its theoretical advantages are discussed. A mathematical method for interpreting the elimination rate is presented. Two modes of intermittent calf compression--a slow and a fast pattern--were compared, and also control group without compression. The elimination rate of the radioisotope was slower with compression than without. Possible interpretations and implications of this observation are discussed.

Female↗

Prophylactive treatment with flunisolide after polypectomy.

Twenty-two patients with nasal polyps completed a double-blind study with a new topical corticosteroid, flunisolide. Treatment during three months after operation gave, in comparison with placebo, a statistically significant effect on the symptom of stuffy nose, and on the sum of scores for stuffy nose, runny nose and sneezing. There was no significant effect on rhinomanometry. Side effects were negligible. Three patients in the placebo-group required a further operation within one year but none in the flunisolide group. Prophylactic treatment with flunisolide can be recommended as a complement to other treatment after surgery of nasal polyps.

Administration, Topical↗